Could HE4 level measurements during first-line chemotherapy predict response to treatment among ovarian cancer patients?

PLoS One. 2018 Mar 27;13(3):e0194270. doi: 10.1371/journal.pone.0194270. eCollection 2018.

Abstract

Background: This study assessed the prognostic value of HE4 marker measurements at various stages of first-line chemotherapy for ovarian cancer.

Methods: The study consisted of 90 ovarian cancer patients, including 48 women undergoing primary surgical treatment and 42 patients qualified for neoadjuvant chemotherapy. Each patient underwent HE4 and CA 125 level measurements at the time of diagnosis and subsequently as follows: after surgical treatment, after the third course of adjuvant chemotherapy, before interval cytoreductive surgery and after chemotherapy. The HE4 value was assessed based on the PSF, OS, DFS, surgical outcome, two-year survival and platinum sensitivity.

Results: Preoperative HE4 levels were a predictor of platinum sensitivity (AUC- 0.644; p = 0.035) and DFS (AUC = 0.637; p = 0.0492). A univariate logistic regression analysis showed that serum HE4 significantly correlated with PFS (baseline results over median HR = 2.96, p = 0.0009; baseline over 75 percentile HR = 2.44, p = 0.0062; normalization after treatment HR = 0.46, p = 0.0125; 50% reduction before IDS HR = 0.64, p = 0.0017). In the multivariate analysis, normalization after treatment and 50% reduction before IDS significantly influenced the PFS (HR = 0.29, p = 0.00008; HR = 0.23, p = 0.0024). The HE4 levels also correlated with the OS as follows: values below the median (HR = 1.88, p = 0.0087), normalization after chemotherapy (HR = 0.08, p = 0.0003), and 50% reduction before IDS (HR = 0.39, p = 0.0496).

Conclusions: The significant effect of the normalization of the HE4 marker after therapy and 50% reduction of HE4 levels before interval cytoreductive surgery on PFS and OS confirmed that HE4 might be an independent prognostic factor of treatment response. HE4 measurements performed during first-line treatment of ovarian cancer may have prognostic significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor*
  • CA-125 Antigen / blood
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Female
  • Humans
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Proportional Hazards Models
  • Proteins / metabolism*
  • ROC Curve
  • Treatment Outcome
  • WAP Four-Disulfide Core Domain Protein 2

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human

Grants and funding

The study was supported by grants No WLA-119-01/S/12/2016 from Pomeranian Medical University of Szczecin, Poland.